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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 15  |  Issue : 5  |  Page : 19-26

Diagnosis of spondyloarthritis: Application of criteria in clinical practice


1 Department of Rheumatology, Gleneagles Global Health City, Chennai, Tamil Nadu, India
2 Centre for Rheumatology, Calicut, Kerala, India

Date of Web Publication23-May-2020

Correspondence Address:
Dr. Vinod Ravindran
Centre for Rheumatology, Calicut - 673 009, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-3698.284747

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  Abstract 


Spondyloarthritis (SpA) is an umbrella term for a group of inflammatory musculoskeletal conditions characterized by predominant involvement of the spine, the lower limb joints, and the entheses. The Assessment of SpA International Society (ASAS) group classifies SpA into axial SpA (axSpA) and peripheral SpA. axSpA was further divided into radiographic SpA and nonradiographic SpA. Classification criteria are meant for research purposes to enroll a homogeneous cohort, unlike diagnostic criteria, which are meant for diagnosing diseases in the community and therefore must include all the heterogeneous manifestations of a disease. Inflammatory low back pain is one of the most important features in history to be elicited in the diagnosis of axSpAs. It should not be used in isolation and always combined with other features of SpA. Magnetic resonance imaging (MRI) is the gold standard and is the only imaging modality capable of detecting both inflammatory and structural changes. A positive MRI finding should be interpreted in the relevant clinical context, and an alternative differential diagnosis for sacroiliitis should be considered if the clinical picture is atypical of SpA. The presence of HLA B 27 in isolation is neither diagnostic of SpAs nor its absence rules out the diagnosis. Erythrocyte sedimentation rate and C-reactive protein are the commonly used biomarkers in SpA but do not always correlate with disease activity. The ASAS criteria have been tested for its validity, though there were concerns regarding its specificity. In this narrative review various criteria available for classifying SpAs have been discussed and their strengths, weaknesses, and usefulness in the diagnosis of SpA in our everyday practice have been appraised . Various referral strategies and usefulness of these criteria and parameters in the Indian context have also been discussed.

Keywords: Ankylosing spondylitis, axial spondyloarthritis, classification criteria, HLA B 27, magnetic resonance imaging, sacroiliitis


How to cite this article:
Santhanam S, Ravindran V. Diagnosis of spondyloarthritis: Application of criteria in clinical practice. Indian J Rheumatol 2020;15, Suppl S1:19-26

How to cite this URL:
Santhanam S, Ravindran V. Diagnosis of spondyloarthritis: Application of criteria in clinical practice. Indian J Rheumatol [serial online] 2020 [cited 2020 May 29];15, Suppl S1:19-26. Available from: http://www.indianjrheumatol.com/text.asp?2020/15/5/19/284747




  Introduction Top


Spondyloarthritis (SpA) is a chronic inflammatory disease which predominantly affects the spine, the lower limb joints, and the entheses. It is an umbrella term which encompasses ankylosing spondylitis (AS), psoriatic arthritis, reactive arthritis, inflammatory bowel disease-associated arthropathy, undifferentiated spondyloarthropathy, and juvenile idiopathic arthritis (enthesitis-related arthritis).[1],[2] In 2009, the Assessment of SpA International Society (ASAS) group published guidelines for the classification of SpA into axial SpA (axSpA) and peripheral SpA. axSpA was further divided into radiographic SpA (earlier referred to as AS before) and nonradiographic SpA (nr-SpA). In nr-SpA, we have two groups – first is sacroiliitis detected only on magnetic resonance imaging (MRI) with normal radiographs and second is a clinical arm with HLA B 27 positivity and coexisting SpA features.[3] ASAS group came out with a separate criteria for peripheral SpA to include patients with features of SpA, but without sacroiliitis.[4] A The diagnosis of SpA need to be made by a combination of clinical, radiological, and laboratory findings. In axSpA, presence of sacroiliac (SI) joint involvement is strongly supportive of the diagnosis. With the introduction of MRI, SpA should ideally be picked up at an earlier stage enabling early initiation of treatment, but still there is a diagnostic delay in the community.[2] With the spectrum of clinical manifestations in SpA being so heterogeneous, are the current classification criteria good enough to pick up all cases in the community? How valid and useful are the classification criteria in daily clinical practice for diagnosing SpA? To answer these questions, in this narrative review, we have discussed the various criteria available for classifying SpAs and have appraised their strengths, weaknesses, and usefulness in the diagnosis of SpA in our everyday practice. We have also discussed various referral strategies and usefulness of these criteria and parameters in the Indian context.


  Search Strategy Top


We searched in PubMed/Medline and Scopus using the terms SpA, nr-SpA, AS, sacroiliitis, classification criteria, diagnostic criteria, and inflammatory back pain. Only articles in the English language were appraised. The majority of articles included was published in the past 10 years with exception of few landmark articles prior to that.


  Classification Criteria for Spondyloarthritis Top


Diagnostic criteria versus classification criteria

In rheumatology, there are criteria for several diseases with majority being classification criteria and only few diagnostic criteria. Before we discuss the various criteria for the classification of SpAs, it would be useful to appreciate the difference between a diagnostic and classification criteria. Diagnostic criteria are used to diagnose a disease with help of clinical signs, symptoms, and investigations. It must be inclusive covering the whole spectrum of the disease and its heterogeneous manifestations. The prevalence and manifestations of a rheumatic disease varies with the geographic area, race, and ethnicity. The sensitivity and specificity of diagnostic criteria needs to be as high as possible (near 100%). Hence, it may be difficult to have uniform diagnostic criteria for a varied patient population.[5] Classification criteria, on the other hand, are uniform definitions with high specificity intended only for research and study purposes. Hence, diagnosis of a disease depends on the judgment of an individual clinician who does it with the help of clinical examination and investigations. Hence, a classification criterion should never influence the diagnosis and treatment decisions.

Evolution of various criteria for classification of spondyloarthritis

The first criteria for AS was proposed in 1963 at the Rome conference as a diagnostic criteria for AS. According to these criteria, patient can be classified as AS even without imaging the SI joint.[6] It was later modified in 1966 and referred to as the New York criteria for AS. In 1984, the New York criteria was again modified by including the Rome criteria for low back pain which was more appropriate than the 1966 New York criterion for pain. Similarly, minor changes were made to “limitation of motion of lumbar spine” and “reduced chest expansion” criterion.[7] The details of all the three criterion are discussed in [Table 1]. Later in 1990s came the Amor [Table 2] and European Spondyloarthropathy Study Group (ESSG) Criteria [Table 3] for classification of spondyloarthropathy, which included the entire spectrum of SpAs. The subgroup of patients who did not satisfy the individual set of criteria for AS, psoriatic arthritis, reactive arthritis, etc., were classified as “Undifferentiated spondyloarthropathy.” Other manifestations of SpAs such as enthesitis and dactylitis were considered along with serology (HLA B27) and treatment response to nonsteroidal anti-inflammatory drugs. The concept of peripheral SpA was also introduced with mention of “asymmetric, predominant lower limb arthritis.”[8],[9]
Table 1: Rome criteria (1963), New York criteria (1966) and modified New York criteria (1984) for classification of ankylosing spondylitis

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Table 2: Amor criteria for classification of spondyloarthritis

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Table 3: European spondyloarthropathy study group criterion for the classification of spondyloarthropathy

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Then, in 2009 came the ASAS classification criteria for both axial [Table 4] and peripheral SpA [Table 5]. The introduction of MRI to detect sacroiliitis has revolutionized the management of SpAs as earlier radiographic criterion used to pick up only structural changes which were chronic in nature. With MRI, acute inflammation (e.g.,: bone marrow edema) are also picked up and therefore, the concept of “nr-SpA” was introduced. For the first time, HLA B27 (part of clinical arm) was used to classify SpAs. The sensitivity and specificity of the new criteria as a whole was 82.9% and 84.4%, respectively, with 66.2% and 97.3%, respectively, for the imaging arm.[3],[4]
Table 4: Assessment of spondyloarthritis International Society classification criteria for axial spondyloarthritis

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Table 5: Assessment of spondyloarthritis International Society classification criteria for peripheral spondyloarthritis

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Inflammatory back pain

Inflammatory low back pain (IBP) is the most important history to be elicited in the diagnosis of axSpAs and it is the common presenting symptom in many patients. In 1977, Calin et al. described the first set of criteria for IBP followed by the Berlin criteria for IBP.[10],[11] Later in 2009, an expert committee of ASAS developed the IBP classification criteria.[12] The various criteria for IBP are discussed in [Table 6]. In a retrospective population-based cohort study, among 124 patients with new-onset IBP, only 39 patients progressed to SpA after a median follow-up of 13.2 years and 58 had resolution of IBP. In this study, IBP resolved in majority and progressed in few, which explained the difference in the prevalence of SpA (0.4%–1.3%) and IBP (3%–6%).[13] The actual sensitivity of IBP criteria depends on the pretest probability of having the disease. The prevalence of SpA in patients presenting with IBP to a rheumatologist is high (25%–50%) in comparison to a general practitioner (<5%). The sensitivity of IBP for SpA diagnosis is only around 70% and hence, chronic low back pain has been used as entry criterion in the ASAS criteria for axSpA. Hence in the diagnosis of axSpA, presence of IBP should not be used in isolation and always combined with other features of SpA.[14]
Table 6: Comparison of various criteria for inflammatory back pain

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Imaging

Currently, one of the most important criteria is documentation of sacroiliitis by radiograph or MRI. Conventional radiographs to detect sacroiliitis were included in the modified New York criteria.[15] Later, introduction of MRI for imaging the SI joints revolutionised the field of spondyloarthritides. In the sacroiliac magnetic resonance computed tomograph (SIMACT) study, T1-weighted MRI when compared with standard radiograph for detecting structural changes in SI joints was found to be superior.[16] For detecting active changes like bone marrow edema, MRI is the gold standard and hence included in the ASAS classification criteria. MRI is the only imaging modality capable of detecting both inflammatory and structural changes.[3]

There have been concerns that usage of MRI leads to over diagnosis. There is evidence for MRI lesions typical of SpA to be found even in healthy individuals.[17] In a Dutch study, sacroiliitis on MRI as per the ASAS definition was found in significant proportion of postpartum women, healthy individuals, and runners (57%, 23%, and 13%).[18] In another study, bone marrow edema and fat metaplasia were observed in MRI of SI joints of hockey players and recreational runners. Erosions and ankyloses of SI joints were rarely observed in healthy individuals. Extensive bone marrow edema was noted in higher proportion of axSpA patients.[19] In another study, sclerosis, osteophytes, and fat metaplasia were observed in non-SpA population, but erosions were never seen. Similarly, the extent of fat metaplasia increased with age.[20] A positive MRI finding should aid in the diagnosis of SpA but should not be the only decisive factor. Recently, Braun and Baraliakos acknowledged that sacroiliitis, enthesitis, spondylitis may not only occur in patients with SpA.[21] Hence, it is the severity and chronicity of such changes which leads to structural changes and hence the need to look into the causes for chronic inflammation.[21] Recently, ASAS MRI working group has updated some of the MRI definitions for SpA. No changes were made to the current SI joint MRI lesions for ax-SpA. However for lesions such as erosion, fat metaplasia, capsulitis, and enthesitis changes have been made and new definitions were created for fat metaplasia in an erosion cavity, ankylosis, joint space enhancement, etc.[22] In practice, pre- and posttest probabilities must be kept in mind and also the fact that ASAS definition of positive MRI for sacroiliitis was intended for classification purposes and not for clinical use.[23] Further, in practice, a positive MRI finding should be interpreted in the relevant clinical context and an alternative differential diagnoses for sacroiliitis should be considered if clinical picture is atypical of SpA.

Serology

We have very limited biomarkers for SpA, one is HLA B27 and other is acute-phase reactants (erythrocyte sedimentation rate/C-reactive protein [ESR/CRP]). HLA B27 is part of the clinical arm in ASAS criteria.[3] However, the presence of HLA B 27 in isolation is neither diagnostic of SpA nor its absence rules out the diagnosis.[2] The prevalence of axSpA depends on the prevalence of HLA B27 in the population. In the Caucasian population, HLA B27 is present in 8% of the population and in the Indian population, it varies from 3% to 6%.[2],[24] In India, the prevalence of HLA B27 positivity varies between 78% and 94% in AS and 85.4%–92% of those diagnosed with nr-SpA are HLA-B27 positive.[25],[26],[27] In a study by van Lunteren et al., 1818 patients from ASAS, DESIR, and SPACE cohorts with suspected axial-SpA were analyzed. They found positive family history was not associated with axial-SpA independent of HLA B27, which, in turn, reinforces the importance of HLA B27.[28]

ESR and CRP are the commonly used biomarkers in SpA similar to other inflammatory arthritides. However, they both have low sensitivity and specificity and does not always correlate with disease activity.[2],[15],[29] CRP levels are elevated in only 40% of patients and may vary with time. Hence in axial-SpA CRP may be repeated (after 4 weeks) on follow-up if the baseline levels are normal as it can turn positive later.[30] CRP has been included in ASAS criteria for SpA and as a part of ASDAS to assess disease activity. High sensitivity CRP is found to correlate better with disease activity than routine CRP.[31] Elevated CRP levels are considered to be a risk factor for structural progression in axSpA and elevation of inflammatory markers is more in AS in comparison to nr-SpA.[32]

Performance and validity of criteria

ASAS assessed the performance of axSpA criteria in a multicenter cohort study of 649 patients.[33] In comparison to ESSG and AMOR criteria, ASAS criteria had similar sensitivity but better specificity (84% vs. 65%–78%). The positive predictive value of the imaging and clinical arms in combination and isolation ranged between 86% and 96%.[33]

In a US cohort of adults aged between 18 years and 45 years with chronic back pain, the sensitivity of ASAS criteria was 47% and specificity was 79%. The cohort had a lower prevalence of males and HLA B27 positivity and hence the lower specificity.[34] In a meta-analysis of seven observational cohorts, the performance of ASAS axSpA criteria was assessed.[35] The pooled specificity was 87%, with the specificity of imaging arm ranging between 74% and 99% and the clinical arm between 71% and 97%. This study demonstrated overall good specificity for the ASAS criteria which is important for identifying a homogeneous population.[35]

In the ASAS – COMOSPA study, which was a multinational cross-sectional study with 3942 patients most of the patients with axSpA fulfilled all the classification criteria with 71.4% fulfilling the Amor, ESSG and ASAS axSpA criteria. Patients fulfilling both the clinical and imaging arm of ASAS axSpA criteria had similar presentations of disease features. This study confirmed the credibility of the criteria with no major inter-regional differences.[36] A study of patients with back pain from eight different cohorts confirmed that terms AS and radiographic SpA can be used interchangeably.[37] To validate the ASAS classification criteria, the SPARTAN and ASAS groups have recently decided to run the “Classification of axSpA Inception Cohort” study.[15]

Concerns regarding the axial spondyloarthritis criteria

The main concern has been regarding the lack of specificity and the potential of over diagnosis, particularly in the clinical arm. One of the concerns was about over diagnosing women with fibromyalgia as SpA. In a study by Baraliakos et al., only 2% of fibromyalgia patients satisfied the ASAS criteria for axSpA. Overall, this study goes a long way in addressing concerns regarding over diagnosis of fibromyalgia as SpA.[38]

In October 2013, the United States Food and Drug Administrations (FDA) rejected the application for Certolizumab and Adalimumab use in the treatment of nr-SpA. One of the main concerns of the FDA was regarding the lack of specificity of ASAS classification criteria when erroneously being used for diagnostic purposes. Though later in March 2019, FDA approved Certolizumab as the first biologic for SpA in United States.[39],[40]

Akkoc and Khan have compared the patient population enrolled in randomized controlled trials (RCTs) of tumor necrosis factor (TNF) inhibitors in nr-SpA with those of the major RCTs of AS. They found that there was lack of homogeneity between the imaging and clinical arms with less percent of males, lower CRP levels, and very high HLA B27 positivity in the clinical arm.[39]

Recently the ASAS criteria were applied in a combined Norwegian and Dutch study. The prevalence of axSpA was 8.4% in the Norwegian study and 23.6% in the Dutch study. Other parameters like HLA B27 and the proportion of males were also different. This highlights the heterogeneity between various populations on application of the ASAS classification criteria.[39]

As discussed in the imaging section, there have been concerns regarding the specificity of MRI criteria in the imaging arm. The prevalence of axSpA in the ASAS cohort was 60% in comparison to the low prevalence (5%) of chronic back pain in the community. So applying the less specific ASAS criteria in the community may lead to lot of false positives. The current criteria do not weigh each parameter based on their ability to confer increased risk of developing SpA, unlike for example, the classification criteria for systemic sclerosis.[39],[40]

The concept of having separate criteria for axSpA and peripheral SpA has also been questioned, as they are two entities of the same diseases with no clear boundaries. In the ASAS cohort, one-third of patients with axSpA had peripheral arthritis in the past and in the peripheral SpA group, 14.2% had a past history of IBP. There is limited evidence to suggest that the response of radiographic SpA and nr-SpA to TNF inhibitors may vary. It needs to be checked whether the varied response is due to misclassification of the categories or difference in their pathogenesis.[40]


  Referral Strategies Top


In spite of all the classification criteria and use of MRI, there is still a significant delay in diagnosing SpAs. In a recent review by Jovaní et al., the average diagnostic delay was stated to be 7 years, with 6.5 years in men and 8.8 years in women. Hence, we need good referral strategies which can be applied at the primary care for diagnosing these diseases. Most of the criteria and the population they were tested are different from the one seen by a primary care physician.[41]

In Leiden SpA Caught Early (SPACE) cohort, 13 referral strategies (models to refer patient to a rheumatologist) were tested.[42] These strategies have been discussed in brief in [Table 7]. Most of the referral strategies did well but the cohort in this study comprised patients already referred to a rheumatology outpatient clinic hence may overestimate the performance of various referral strategies. Later, Sepriano et al. proposed a EpiReumaPt referral strategy which was tested in the general population where the prevalence of SpA was low unlike the previous study in SPACE cohort.[43] The EpiReumaPt referral strategy performed well as a screening tool in the general population and has been discussed in [Table 7].
Table 7: Comparison of Epi ReumaPt, Assessment of Spondyloarthritis International Society, brandt1, radar/3 and master referral strategies based on Carvalho et al[2]

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  Indian Context Top


In the community low back pain is a common symptom. A Community Oriented Program from Control of Rheumatic Diseases survey showed the rural prevalence of back pain to be 17.3%. Of these, 1%–2% were likely to develop SpA and hence, the prevalence was calculated to be around 0.17%–0.34%.[44] Hence, in clinical practice, this small percentage of cases of SpA needs to be picked up among the various causes of back pain. In primary care, patients presenting with inflammatory back pain need to be screened and when necessary to be referred to a rheumatologist. Creating awareness among primary care physicians and providing them with an easy and feasible referral pathway is the key. We should also remember the cost involved in getting a MRI and HLA B 27 testing done in Indian setting and hence to be used in the right clinical context.[45] We propose an algorithm [Figure 1]for both the primary care physicians and the rheumatologist for the diagnosis of SpA in the Indian setting.
Figure 1: Flow chart to screen and diagnose Spa in daily practice

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  Conclusion Top


Various classification criteria for SpAs have different individual components, their own pros and cons and variability in both their performance and validity. They are continuously evolving on the face of fast developing evidence. As SpAs have varied manifestations, clinician's judgment is extremely important in diagnosing an individual patient. In a resource poor country such as India, we should have our own referral strategy for diagnosing these diseases early in the community.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Abstract
Introduction
Search Strategy
Classification C...
Referral Strategies
Indian Context
Conclusion
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